Dynamics of HIV reservoirs during the use of a two-component regimen with dolutegravir and lamivudine in HIV-infected patients who have not previously received treatment

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Рұқсат ақылы немесе тек жазылушылар үшін

Аннотация

Objective. Assesment of the dynamics of HIV reservoirs during the use of a two-component antiretroviral therapy (ART) regimen with dolutegravir and lamivudine (DTG + 3TC) in previously untreated patients.

Materials and methods. The study included 30 HIV-positive patients over 18 years of age, monitored in the AIDS Consultation and Diagnostic Department of the Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, who first started treatment with the DTG + 3TC regimen in 2021–2022. A standard clinical and laboratory examination, determination of the immunoregulatory index and HIV DNA in blood cells were performed.

Results. During 48 weeks of ART, no adverse events associated with the study drugs that required changes in the treatment regimen were registered. All patients achieved the virological efficacy criterion by 24 weeks of treatment. The mean CD4+-lymphocyte level before treatment was 526 cells/μl, 24%; after 48 weeks of ART – 747 cells/μl, 34% (p < 0.05), the mean CD4+/CD8+ ratio was 0.55 and 1.06, respectively (p < 0.05). The correlation index (r) of the HIV DNA level in blood cells before the start of ART with HIV RNA in blood plasma was 0.8; with CD4+-lymphocytes – -0.4, with the duration of HIV infection – –0.2. The mean HIV DNA level in blood cells before treatment was 480 copies per 1 million cells, after 48 weeks of ART – 220 copies per 1 million cells (p < 0.05).

Conclusion. The use of the DTG + 3TC regimen in patients who had not previously received ART showed clinical, immunological and virological efficacy for 48 weeks. The HIV reservoir volume before treatment was higher in patients with high viral load and lower CD4+-lymphocyte level. The volume of viral reservoirs decreased with the use of DTG + 3TC.

Толық мәтін

Рұқсат жабық

Авторлар туралы

Anastasia Pokrovskaya

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being; Patrice Lumumba Peoples’ Friendship University of Russia

Хат алмасуға жауапты Автор.
Email: pokrovskaya@cmd.su
ORCID iD: 0000-0002-2677-0404

MD, Senior Researcher, Professor, Department of Infectious Diseases with Courses of Epidemiology and Phthisiology, Medical Institute

Ресей, Moscow; Moscow

Alina Kirichenko

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Email: kirichenko@cmd.su
ORCID iD: 0000-0002-7116-0138

Cand. Med. Sci., Scientific Researcher

Ресей, Moscow

Olga Khokhlova

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Email: xoxlova@cmd.su
ORCID iD: 0000-0001-9736-4043

Cand. Med. Sci., Head, Clinical and Laboratory Group, Doctor of Clinical Laboratory Diagnostics

Ресей, Moscow

Ekaterina Kulabukhova

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being; Patrice Lumumba Peoples’ Friendship University of Russia

Email: ekulabukhova@mail.ru
ORCID iD: 0000-0003-3645-7275

Cand. Med. Sci., Assistant, Department of Infectious Diseases with Courses of Epidemiology and Phthisiology, Medical Institute, Infectious Disease Specialist

Ресей, Moscow; Moscow

Marina Goliusova

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Email: mad2501@yandex.ru
ORCID iD: 0000-0002-5325-6857

Infectious Disease Specialist

Ресей, Moscow

Dmitry Kireev

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Email: Dmitkireev@yandex.ru
ORCID iD: 0000-0002-7896-2379

Cand. Biol. Sci., Head, Laboratory of Diagnostics and Molecular Epidemiology of HIV infection

Ресей, Moscow

Oleg Yurin

Central Research Institute of Epidemiology, Russian Federal Service for Supervision of Consumer Rights Protection and Human Well-Being

Email: oleg_gerald@mail.ru
ORCID iD: 0000-0002-9290-9048

Leading Researcher

Ресей, Moscow

Әдебиет тізімі

  1. ВИЧ-инфекция у взрослых. Клинические рекомендации. Национальная ассоциация специалистов по профилактике, диагностике и лечению ВИЧ-инфекции, Национальная вирусологическая ассоциация, 2020. https://cr.minzdrav.gov.ru/recomend/79_1 [HIV infection in adults. Clinical guidelines. National Association of Specialists in the Prevention, Diagnosis and Treatment of HIV Infection, National Virological Association], 2020. (In Russ.). https://cr.minzdrav.gov.ru/recomend/79_1
  2. Покровский В.В., Юрин О.Г., Кравченко А.В., Беляева В.В., Ермак Т.Н., Шахгильдян В.И. и др. Рекомендации по лечению ВИЧ-инфекции и связанных с ней заболеваний, химиопрофилактике заражения ВИЧ. Эпидемиол. инфекц. болезни. Актуал. вопр. 2022; 12(4, приложение). 108 с. Pokrovsky V.V., Yurin O.G., Kravchenko A.V., Belyaeva V.V., Ermak T.N., Shakhgildyan V.I. et al. [Recommendations for the treatment of HIV infection and related diseases, chemoprophylaxis of HIV infection]. Epidemiology and infectious diseases. Current items 2022; 12(4, application). 108 р. (In Russ.).
  3. Department of Health and Human Services USA. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. 2023. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf
  4. European AIDS Clinical Society. Guidelines, Version 11.0, October 2021. https://www.eacsociety.org/media/final2021eacsguidelinesv11.0_oct2021.pdf
  5. WHO. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV, 2018. https://www.who.int/publications/ i/item/WHO-CDS-HIV-18.51
  6. Aydin E., Yilmaz Aydin F., Demir Y., Yildirim Y., Celen M.K. Evaluation of kidney function tests in HIV‐positive patients receiving combined antiretroviral therapy. Int. J. Clin. Pract. 2021; 75(8): e14542. doi: 10.1111/ijcp.14542
  7. Estrada V., Domingo P., Suarez-Lozano I. Risk of cardiovascular disease in patients with HIV infection undergoing antiretroviral therapy. Revista Clínica Española (English Edition) 2020; 220(3): 149–54. doi: 10.1016/j.rceng.2019.05.012
  8. Nduka C.U., Stranges S., Kimani P.K., Sarki A.M., Uthman O.A. Is there sufficient evidence for a causal association between antiretroviral therapy and diabetes in HIV-infected patients? A meta-analysis. Diabetes Metab. Res. Rev. 2017; 33(6): e2902. doi: 10.1002/dmrr.2902
  9. Back D., Marzolini C. The challenge of HIV treatment in an era of polypharmacy. J. Int. AIDS Soc. 2020; 23(2): e25449. doi: 10.1002/jia2.25449
  10. Беляева В.В., Козырина Н.В., Соколова Е.В., Семикова С.Ю., Галиулин Н.И., Лебедева Е.П. и др. Анализ факторов риска нарушения приверженности диспансерному наблюдению и лечению ВИЧ-инфекции: оценка готовности следовать рекомендациям специалистов. Эпидемиол. инфекц. бол. Актуал. вопр. 2021; 11(3): 63–8. doi: 10.18565/epidem.2021.11.3.63-8 Belyaeva V.V., Kozyrina N.V., Sokolova E.V., Semikova S.Yu., Galiullin N.I., Lebedeva E.P. et al. [Analysis of risk factors for non-adherence to follow-up and treatment for HIV infection: assessment of readiness to follow specialists’ recommendations]. Epidemiology and infectious diseases. Current items 2021; 11(3): 63–8. (In Russ.). doi: 10.18565/epidem.2021.11.3.63-8
  11. Girouard M.P., Sax P.E., Parker R.A., Taiwo B., Freedberg K.A., Gulick R.M. et al. The cost-effectiveness and budget impact of 2-drug dolutegravir-lamivudine regimens for the treatment of HIV infection in the United States. Clin. Infect. Dis. 2016; 62(6): 784–91. doi: 10.1093/cid/civ981
  12. Cahn P., Madero J.S., Arribas J.R., Antinori A., Ortiz R., Clarke A.E. et al. Durable efficacy of dolutegravir plus lamivudine in antiretroviral treatment–naive adults with HIV-1 infection: 96-week results from the GEMINI-1 and GEMINI-2 randomized clinical trials. Journal of Acquired Immune Deficiency Syndromes (JAIDS) 2020; 83(3): 310–8. doi: 10.1097/qai.0000000000002275
  13. Кижло С.Н., Man C.Y., Sievers J., Urbaityte R., Brown D., Кузнецов С.Д. и др. Применение долутегравира и ламивудина в сравнении с применением долутегравира и тенофовира/эмтрицитабина у ранее не получавших лечения взрослых, инфицированных ВИЧ-1: результаты оценки эффективности и безопасности на 48 неделе у участников исследования GEMINI-1/2 в исследовательских центрах в России. Журнал инфектологии 2019; 11(3, приложение 1): 131–2. doi: 10.22625/2072-6732-2019-11-3 Kizhlo S.N., Man C.Y., Sievers J., Urbaityte R., Brown D., Kuznetsov S.D. et al. [Dolutegravir and lamivudine versus dolutegravir and tenofovir/emtricitabine in previously untreated HIV-1 infected adults: 48-week efficacy and safety results in participants in the GEMINI-1/2 study at research centers in Russia]. Journal of Infectology 2019; 11(3, application 1): 131–2. (In Russ.). doi: 10.22625/2072-6732-2019-11-3
  14. Квасов Н.А., Полякова А.К., Лопатухин А.Э., Мурзакова А.В., Шемшура А.Б., Киреев Д.Е. Метод измерения размера клеточного резервуара ВИЧ и определение его у пациентов без опыта приема АРТ. Эпидемиол. инфекц. болезни. Актуал. вопр. 2021; 12(4): 66–72. doi: 10.18565/epidem.2021.11.4.66–72 Kvasov N.A., Polyakova A.K., Lopatukhin A.E., Murzakova A.V., Shemshura A.B., Kireev D.E. [Method for measurement of the size of the HIV cell reservoir and for its determination in patients who are not experienced with ART]. Epidemiology and infectious diseases. Current items 2021; 12(4): 66–72. (In Russ.). doi: 10.18565/epidem.2021.11.4.66–72
  15. Веселова Е.И., Каминский Г.Д., Карамов Э.В., Кудлай Д. А., Орлова-Морозова Е. А., Ловачева А. Г. и др. Эффективность и безопасность лечения ВИЧ-инфекции с переходом на битерапию после 24 недель тритерапии. Инфекционные болезни: новости, мнения, обучение 2021; 10(4): 66–75. doi: 10.33029/2305-3496-2021-10-4-66-75 Veselova E.I., Kaminsky G.D., Karamov E.V., Kudlay D. A., Orlova-Morozova E. A., Lovacheva A. G. et al. Switching to dual therapy after 24 weeks of the triple therapy of HIV infection: efficacy and safety. Infectious diseases. News, opinions, training 2021; 10(4): 66–75 (In Russ.). doi: 10.33029/2305-3496-2021-10-4-66-75
  16. Moreno S., Perno C.F., Mallon P.W., Behrens G., Corbeau P., Routy J.P. et al. Two-drug vs. three-drug combinations for HIV-1: Do we have enough data to make the switch? HIV Med. 2019; 20, Suppl 4: 2–12. doi: 10.1111/hiv.12716
  17. Llibre J.M., Cahn P.E., Lo J., Barber T. J., Mussini C., van Welzen B. J. et al. Changes in Inflammatory and Atherogenesis Biomarkers With the 2-Drug Regimen Dolutegravir Plus Lamivudine in Antiretroviral Therapy–Experienced, Virologically Suppressed People With HIV-1: A Systematic Literature Review. Open. Forum Infect. Dis. 2022; 9(4): ofac068. doi: 10.1093/ofid/ofac068
  18. Kireev D., Kvasov N., Murzakova A., Kirichenko A., Pokrovskaya A., Shemshura A. Association of viral reservoir with HIV infection duration, viral load and CD4 count. Abstract P_62, p. 63. Reviews in Antiviral Therapy & Infectious Diseases 2020_7, 18th European Meeting on HIV & Hepatitis Treatment Strategies & Antiviral Drug Resistance, 28-30 October 2020, virtual meeting.
  19. Moh D.R., Ntakpé J.B., Gabillard D., Yayo-Emieme A.A., Badjé A., Kouame G.M. et al. Association of cellular HIV-1 DNA and virological success of antiretroviral treatment in HIV-infected sub-Saharan African adults. BMC Infect. Dis. 2022; 22: 100. doi: 10.1186/s12879-022-07082-2
  20. Blazkova J., Whitehead E.J., Schneck R., Shi V., Justement J. S., Rai M. A. et al. Immunologic and Virologic Parameters Associated with Human Immunodeficiency Virus (HIV) DNA Reservoir Size in People With HIV Receiving Antiretroviral Therapy. The Journal of Infectious Diseases 2024; 229(6):1770–1780. doi: 10.1093/infdis/jiad595

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2. Fig. 1. Individual dynamics of HIV DNA level in cells while taking DTG + 3TC Dotted line - mean value.

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